Pharmacokinetic-pharmacodynamic evaluation of a fraction with a neuroprotective activity of Tagetes lucida

Abstract

Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system (CNS) and inflammatory ailments. Among the compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenylscopoletin (PE), scoparone (SC), dimethylfraxetin (DF), herniarin (HR), and 7-O-prenylumbelliferone (PU). Therefore, the relationship between the therapeutic effect and the concentration can be evaluated through pharmacokinetic-pharmacodynamic (PK–PD) studies under a model of neuroinflammation induced by lipopolysaccharide (LPS). In the present study, a bioanalytical method was established by HPLC-UV for the simultaneous quantification of the coumarins present in the active fraction of T. lucida, which was able to determine the temporal concentration profiles of each of the coumarins in the plasma, brain, kidney, and spleen samples of healthy and damaged mice. Coumarins showed an increase in plasma concentrations of up to three times in the neuroinflammation model, compared to healthy mice, so it was possible to quantify the therapeutic agents in the main target organ, the brain. The ability of compounds to cross the blood-brain barrier is an advantage in the treatment of diseases associated with neuroinflammation processes, A pertinent assay that was proposed in the present investigation with T. lucida, is the measurement of the extravasation of the Evans blue dye in the brain of mice, with and without LPS, that causes neuroinflammation and an increase in the permeability of the blood-brain barrier. Future PK-PD assessments at different doses and longer test times are proposed to obtain parameters that determine the best possible effect without toxic responses.